We seek to capitalize on a substantial body of work that has characterized the immune responses of HIV+ individuals with very slow disease progression (LTNP), and HIV- individuals who do not seroconvert despite repeated HIV exposure (ESN). A fraction of people in these groups produce natural anti-CCR5 antibodies that are associated with their disease-free status (in longitudinal studies loss of these antibodies results in disease progression). These antibodies are unique in that they bind rare CCR5 epitopes, induce a long term downregulation of CCR5 on the surface of cells, and can inhibit transcytosis of HIV across mucosal membranes. Experimentally raised polyclonal chicken antibodies to these epitopes are even more potent than their human-derived counterparts with respect to these biological activities, and represent an opportunity to develop a unique product offering in the HIV/AIDS arena. We will use our proprietary technology to raise a panel of chicken monoclonal antibodies to these CCR5 epitopes and humanize the most active members of this panel for further development.